Diquaternary bis-[4-alkylthiopyridyl-(1)]-alkanes



3,101,342 DIQUATERNARY BES-I l-ALKYLTHIO- rrnmrr-nn-atxarsus KlausThomas and Dietrich .lerchel, Biberach an der Riss, Germany,

tion of Germany No Drawing. Filed May 9, 1961, Ser. No. 108,770

Claims priori application Germany Mayl l, 1%!) 8 Claims. (Cl. 260294.8)

This invention relates to cliquaternary bis-[4-alkylthiopyridyl-(DJ-a-lkanes as well as to a method of preparingsuch compounds.

More particularly, the present invention relates to diquaternarycompounds of the formula RI! RI! wherein The diquaternary compoundsaccording to the present invention are most conveniently prepared byreacting a 4-alkylthio-pyridine of the formula wherein R and R have themeanings previously defined in connection with Formula I, with acompound of formula A--RA (111) wherein A and R also have the meaningspreviously defined in connection with Formula I. The reaction is carriedout by heating a mixture of the starting materials to elevatedtemperatures, preferably to temperatures above 100 C. and below thedecomposition temperature of the reaction components, and advantageouslyin the presence of .an inert organic solvent, such as an alcohol, anarcmatic hydrocarbon, dioxane and the like. Two mols of the4-alkylthio-pyridine are used for each mol of Compound III. The inertsolvent medium should preferably be one which has a boiling point above100 C., so that the optimum reaction temperature coincides with theboiling point of the particular solvent. In theevent that the boilingpoint of Compound III and/or of the inert solvent is below 100 0., thereaction may be carried out at elevated pressures so as to raise theboiling point of the reaction mixture above 100 C.

The reaction mixture is worked up by evaporating the inert solvent andrecrystallizing or reprecipitating the residue. The yields of thepurified end products are about 3060% of theory. 1

The 4-alkylthio-pyridines (II) used as one of the start ing materialsare either well known compounds or may be prepared by known methods,such as by the method described in Chernische Berichte, vol. 89, page2923 (1956).

The following examples. illustrate the preparation of a fewrepresentative members of the group of .diquaternary compounds embracedby Formula I above. It will be understood, however, that ,these examplesare given for purposes of illustration only and that the presentinvention is not limited to these examples.

assignors to Dr. Karl Thomae G.m.h.H., Biherach an der Riss, Germany, acorpora n01 and ether.

3,101,342. Patented Aug. 20, 1963 EXAMPLE I 1,4-Bis- [4- n-Cetyl-Thi0)-Pyridinium-(1 1-n-Butane Dibromide A mixture of 5 gm. of4-(n-cetyl-thio)-pyridine, 1.65 gm. of 1,4-dibromo-butane and 50 cc. ofbutanol was heated for six hours at 115" C. Thereafter, the butanol wasdistilled oil. in vacuo and the residue was repreoipitated firom amixture of methanol and ether. 3 gm. of the diquaternary compound of theformula were obtained. The product had a melting point of 138 C.(decomposition).

EXAMPLE II 1,10-Bz's- [4'-(n-Butyl-Thi0) -Pyridinium-(1 ]-n-DeczmeDibromide A mixture of 8.35 gm. of 4-(n-butyl-thio)-pyridine, 7.5 gm. of1,:10-dibromo-n-decane and cc. of butanol was heated for six hours at C.Thereafter, the reaction mixture was concentrated by evaporation invacuo, and the residue was reprecipitated from a mixture of metha- 5 gm.of the diquaternary compound of the formula were obtained. The producthad a melting point of 108-110" C.

EXAMPLE III 1,6-Bis- [4- (n-Cetyl-Thi0) -Pyrz'dinium- (1 ]-n-HexaneDibromide were obtained. The product decomposed at 230 C.

EXAMPLE 1V 1 ,2-Bz's- [4 (n-Cetyl-T hi0) -Pyridini um- (I ]-EthaneDibromide A mixture of 17 gm. of 4-(n-cetyl-thio)-pyridine, 4.5 gm. of1,2- dibromc-ethane and 50 cc. of n-butanol was refluxed for six hours-After distilling off the butanol and reprecipitating the product from amixture of ethanol and ether, 10 gm. (46.5% of theory) of thediquaternary compound of the formula were obtained. The product had amelting point of 200 C.

EXAMPLE V 1,6-Bis-[3'-Methyl-4 -(n-Cetyl-Thio)-Pyridiniumi (l -n-HexaneDibromide A mixture of 3.5 gm; of 3-methyl-4-(n-cetyl thioy pyr'idine,1.2 gm. of l,6- dibrorno-n-hexane and 70 cc. nbutanol was heated fortwelve hours at C. There after, the butanol was distilled off and theresidue was reprecipitated from a mixture of "ethanol and ether. 2.5

gm. (54% of theory) of the diquaternary compound of al owed to cool,whereby the reaction product precipitated the formula out. Theprecipitate was reprecipitated from a mixture of ethanol and ether,yielding 3 gm. (25% of theory) of having a melting point of 120-122 C.were obtained. The product had a melting point of 154- EXAMPLE X1,10-Bis-[4'-Allyl-Thi0)-Pyridinium-(1)]-n-Decane EXAMPLE VI Dibromide1,10-Bis-[4'(Ethyl-Thio)-Pyridinium-(1')]-n-Decane A mlxture of 8 of4491131141110)? 10 of 1,10-dibromo-n-decane and 50 cc. of acetonitrilewas heated for eight hours at the boiling point. Thereafter, A m'iXtllreof 5 of Y )-P5 E the reaction mixture was concentrated by evaporationand Dibromide of 1,10-dibromo-n-decane and 200 cc. of acetonitrile wasth ti product was i it t d f o the evaporareiluxed for ten hours.Thereafter, the reaction mixture ti id b adding ethylacetafe thereto,135 gm. was concentrated by evaporation, allowed to cool, and (84% ftheory) of the diquaternary compound of the the residue was admixed withether, whereby a precipi formul F xa- LC 2 0 H-GHzS N(C H2) mSCHg-CH=CH2].2B rtate formed which was separated. 3.2 gm. (29% of wereobtained. After reprecipitation from a mixture of theory) of thediquaternary compound of the formula ethanol and ethylacetate theproduct had a melting point H of 109411 c. [n.mmB-wnmut OZH5].3BIEXAMPLE XI ,10-B"- -P 1' were obtained. The raw product had a meltingpoint of 1 i [4 35 x535 g gil gg )1 n 8992 C. It may be purified byreprecipitation from a A mixture of 11.5 gm. of4-(isopropyl-thio)-pyridine, mlxture of ethanol and ether 15 gm. ofl,l0-dibromo-n-decane and 100 cc. of n-bu- EXAMPLE VII tanol wasrefluxed for five hours. After cooling, the reac- 1,10 Bl-s [4(moctyLThio) Pyridmium 1')] n DeCane tion product was precipitated byadding ethylacetate to Dibromide the reaction mixture. 15.5 gm. (68% oftheory) of the A mixture of 12 gm. of 4-(n-ootyl-thio)-pyridine, 14quatggmry compound of the formula CH gm. of 1,10-dibromo-n-decane and 70cc. of acetonitrile a 1 i a was refluxed for three hours. Thereafter,the reaction ?HS 2)1o C 1 Brmixture was admixed with ethylacetate toprecipitate the CH3 C113 reactifln Product, which Was Tepfecipifiatfidfrom a were obtained. The product had a melting point of mixture ofethanol and ethylacetate. 12 gm. (75% of 95 97 C theory) of thediquaternary compound of the formula XAMP X11 1,10-Bis-[4'-(Sec.Butyl-Thio)-Pyridinium-(1')]-n- [E708 Q (0112) s Decane Dibromide wereobtained. The product had a melting point of 96- A mixture of of 44556-butyl'thio)pyridine: C. 2.25 gm. of 1,10-d1bromo-n-decane and 30 cc. ofn-bu- EXAMPLE VH1 tanol was refluxed for eight hours. Thereafter, the

reaction mixture was concentrated by evaporation, the

1,1 O-Bis-[4'-(n-Cetyl-Thio)-Pyridinium-(l residue was allowed to cooland ethylacetate was added D mate thereto to precipitate the reactionproduct. The precipi- Amixture of 4.65 gm. of 4-(n-cetyl-thi'o)pyridine,3.35 tate was reprecipita-ted from a mixture of ethanol and gm. :ofdecamethyleneglycol-(1,10)-di-p-toluene-sulfonate ethylacetate, yielding2.8 gm. (58% of theory) of the diand cc. of xylene was heated for sevenhours 'at quaternary compound of the formula [onkcm-pn sfl-(cm) 10-5-sln-cm cm].znr

CH3 CH3 C. on an oil bath. Thereafter, the reaction mixture was having amelting point of 79-81 C. allowed to cool and was then admixed withethylacetate EXAMPLE XIII to precipitate the reaction product. The rawproduct was 12.13 1 -[4 (n-D decyl-Thi0) -Pyridinium-(l J-Ethanerepeatedly reprecipitated from a mixture of alcohol and Dibmmideethylacetate. 1.35 gm. (17% of theory) of the diquater- A mixture f 5 gmf 4-(n dodecy1 thio) pyridine, 2 nary compound of the formula gm. of1,2-dibromoethane and 40 cc. of acetonitrile was C e [haCm-SC -(C 2)ioNSCl8H33:i .2SO3CH; were obtained. The product had a melting point ofrefluxed for fourteen hours. Thereafter, the reaction 108-110 C. mixturewas allowed to cool, whereby the reaction product precipitated out. Theprecipitate was separated by vac- EXAMPLE IX uum filtration and wasrecrystallized from ethanol. 1.51,10-Bis-[4-(n-Cetyl-Thi0)-Pyridinum-(1)J-n-Decane 70 gm. 20% of theory)of the diquaternary compound of Dibromide the formula 8.5 gm. of4-(n-cetyl-thio)-pyridine were dissolved in [Hzscrs n-butanol, and tothe resulting solution 3.75 gm. of 1,10- dibromo-n-decane were added.The reaction mixture were obtained. The product had a melting point ofwas then refluxed for twelve hours. Thereafter, it was 7 275 C.

ethylacetate to the reaction solution.

EXAMPLE XIV 1,6-Bis-[4-(n-Butyl-Thi0) -Pyridinium-(1 -n-Hexane DibromideA mixture of 4.0 gm. of 4-(n-butyl-thio)-pyridine, 2.9 gm. of1,6-dibromo-n-hexane and 40 cc. of acetonitrile was refluxed forfourteen hours. Thereafter, the reaction mixture was allowed to cool andthen the reaction product was precipitated by adding ether to thereaction solution. The precipitate was separated and reprecipitatedfroma mixture of ethanol and ether. 5.0 gm. (72% of theory) of thediquaternary compound of the formula R is alkylene of 1 to carbon atoms,

were obtained. The product had a melting point of EXAMPLE XV 1 ,8-Bz's-[4 Isopropy l-Thio -Pyridini um- (I -n-Octane Dibromide.

A mixture of 6.1 gm. of 4(isopropyl-thio)-pyridine, I

5.4 gm. of 1,8-dibromo-n-roctane and 40 cc. of dimethylformamide washeated for eight hours at 8090 C. Thereafter, the reaction solution wasallowed to cool, and then the reaction product was precipitated byadding 10.2 grn. (89% of theory) of the diquaternary compound of theformula CH3 C 3 were obtained. The product had a'melting point of140-145 C.

I The diquaternary compounds according to the present invention areuseful in that they exhibit excellent bactericidal and fungicidalproperties, especially against bacteria and fungi which are usuallydifii'cultt-o combat.

For example, the compounds embraced lay-Formula I above are especiallyeffective against Aspergillus niger and Candida albicans. In thisrespect they are Iconsiderably and unexpectedly superior to knownpyridinium compounds. Moreover, the compounds according to the presentinvention exhibit very satisfactory diffusion properties and do not showany incompatibility toward albumin. Consequently, they are eminentlysuited for wherein R is selected from the group consisting of straight obranched chain alkyl of 1 to 16 carbon atoms and alkenyl of 3 carbonatoms,

R" is selected from the group consisting of hydrogen and methyl, and V Ais the anion of an acid selected from the group consisting of hydnohalicacids and p-toluene sulfonic acid.

wherein R is alkylene of 1 to 10 carbon atoms,

R is selected from the group consisting of straight or branched chainalkyl of 1 to 16 carbon atoms and lower alkenyl,

R" is selected afirom the group consisting of hydrogen and lower alkyl,and Y A is the anion of an acid selected from the group consisting ofhydrohalic acids and p-toluene sulfonic acid,

which comprises formula wherein R and R have the meanings defined above,with a'rdisubstituted alkane of the formula A-RA wherein A is selectedfrom the group consisting of puse as active ingredients in disinfectantand fungicidal compositions adapted for employment in the home, in

hospitals as well as in industry.

While we have illustrated our invention the .aid of certain specificembodiments thereof, it will be readily apparent to those skilled in theart that the present invention is not limited solely to those particularembodiments, and that various changes and modifications may be madewithout departing from :the spirit of theinvention or the scope of theappended claims.

We claim: V 1. Diquaternary compounds of the formula reaction is carriedsolvent.

toluyl-sulfonyl' andv halogen and R has therneanings defined above,. ata temperature above C. but below the decomposition temperature of thereactants and re- 7 action product. e V i 8., 'Ihe1proces's according toclaim 7, whereinsaid out in the presence of an inert organic ReferencesCited the file of this patent I .UNITED STATES PATENTS 2,909,527 Shapiroetal." Oct. 20, 1959 Shapiro et al. Oct. 20, 1959 OTHER REFERENCES INoller: Chemistry of Organic Compound, 2nd edition, page 272(1957)(Saunders). v

reacting a 4 -(alkyl-thio)-py-ridine of the r

1. DIQUATERNARY COMPOUNDS OF THE FORMULA